crossing96/oncoscreening huggingface dataset:
Advanced chronic kidney disease; A comparison between nephroureterectomy and nephron-sparing surgery for upper tract urothelial carcinoma.	PURPOSE: Renal function outcomes between radical nephroureterectomy (RNU) and nephron-sparing surgery (NSS) for upper tract urothelial carcinoma (UTUC) patients are not well established. We sought to compare the incidence and factors associated with development of advanced chronic kidney disease (CKD) between RNU and NSS and examine the role of acute kidney injury (AKI) on renal function outcomes. METHODS: We retrospectively analyzed an institutional database for patients who underwent either RNU or NSS for UTUC. Cumulative incidence of postoperative advanced CKD, defined as eGFR < 30 ml/min/1.73 m(2), was compared between groups. Fine-Gray competing risk regression was used to identify predictors of advanced CKD. Locally weight scatterplot smoothing was used to assess postoperative eGFR trends. AKI events were counted, staged, and assessed for influence of progression to advanced CKD. RESULTS: Four hundred and twenty-six patients were included in analysis, with a median follow up of 6.68 years (IQR 3.4-12.2). Median preoperative eGFR was similar between the groups (NSS: 68 ml/min/1.73 m(2), RNU: 65 ml/min/1.73 m(2)(,)P = 0.220). Cumulative incidence of advanced CKD was significantly lower in the NSS cohort (P = 0.009). Factors associated with advanced CKD included age, diabetes, recurrent AKI and RNU. Percent of patients with an AKI event differed between the groups (51.5% NSS, 72.7% RNU, P = <0.001), there was no between group difference in percentage of patients with recurrent AKI (25.6% NSS, 25.9% RNU, P =1). CONCLUSION: NSS provides a renal function benefit in UTUC. AKI is common among UTUC patients and recurrent AKI is a risk factor for development of advanced CKD.	bladder
Evaluation of grade and invasiveness of bladder urothelial carcinoma using infrared imaging and machine learning.	Urothelial bladder carcinoma (BC) is primarily diagnosed with a subjective examination of biopsies by histopathologists, but accurate diagnosis remains time-consuming and of low diagnostic accuracy, especially for low grade non-invasive BC. We propose a novel approach for high-throughput BC evaluation by combining infrared (IR) microscopy of bladder sections with machine learning (partial least squares-discriminant analysis) to provide an automated prediction of the presence of cancer, invasiveness and grade. Cystoscopic biopsies from 50 patients with clinical suspicion of BC were histologically examined to assign grades and stages. Adjacent tissue cross-sections were IR imaged to provide hyperspectral datasets and cluster analysis segregated IR images to extract the average spectra of epithelial and subepithelial tissues. Discriminant models, which were validated using repeated random sampling double cross-validation, showed sensitivities (AUROC) ca. 85% (0.85) for the identification of cancer in epithelium and subepithelium. The diagnosis of non-invasive and invasive cases showed sensitivity values around 80% (0.84-0.85) and 76% (0.73-0.80), respectively, while the identification of low and high grade BC showed higher sensitivity values 87-88% (0.91-0.92). Finally, models for the discrimination between cancers with different invasiveness and grades showed more modest AUROC values (0.67-0.72). This proves the high potential of IR imaging in the development of ancillary platforms to screen bladder biopsies.	bladder
Noninvasive studies may have potential to replace cystoscopy in non-muscle invasive bladder cancer follow-up.	Bladder cancer has a high recurrence rate which requires frequent follow-up. Cystoscopy is currently the gold standard for follow-up which is invasive and undesirable procedure for patients. We aimed to investigate the feasibility of noninvasive studies for follow-up of non-muscle invasive bladder cancer. This retrospective study was done for non-muscle invasive bladder cancer patients with abnormal lesion at follow up cystoscopy, therefore those needed transurethral resection of bladder tumor (TUR-BT). Inclusion criteria was patients who had preoperative bladder magnetic resonance imaging (MRI) within 1 month to TUR-BT and urine cytology results. MRI, urine cytology, and surgical pathology results were analyzed for sensitivity, specificity, positive and negative predictive values, accuracy, diagnostic odds ratio, and number needed to misdiagnose for the diagnostic performance of non-invasive studies. From total of 2,258 TUR-BT cases, 1,532 cases of primary TUR-BT and 481 cases which bladder MRI were not done was excluded. Finally, 245 cases of TUR-BT were included. Combined urine cytology and bladder MRI showed 96% sensitivity, 43% specificity, 89% positive and 67% negative predictive values, 87% accuracy, 16.2 diagnostic odds ratio, and 7.4 number needed to misdiagnose values. Among nine false-negative cases, three (1.2%) were missed by the radiologist, two (0.8%) had an empty bladder during magnetic resonance imaging, and three (1.2%) had gross hematuria which needed cystoscopy despite of bladder MRI or urine cytology result. Only one case (0.4%) was missed based on symptoms and noninvasive tests. However, none of the false-negative cases showed rapid extensive progression requiring radical or partial cystectomy. The combination of bladder MRI and urine cytology was comparable to cystoscopy for the follow-up of recurred lesions in non-muscle invasive bladder cancer patients for sensitivity, but not for specificity. However, it may reduce the need for cystoscopy and allowing patients to have choices for follow up diagnostic methods. Also, additional imaging tests to evaluate kidney, ureter and peri-vesical lesions can be reduced.	bladder
Biodynamic prediction of neoadjuvant chemotherapy response: Results from a prospective multicenter study of predictive accuracy among muscle-invasive bladder cancer patients.	"BACKGROUND: Biodynamic signatures (temporal patterns of microscopic motion within a 3-dimensional tumor explant) offer phenomic biomarkers that are highly predictive for therapeutic response. OBJECTIVE: By utilizing motility contrast tomography, which provides a simple, fast assessment of motion patterns in living tissue, we evaluated the predictive accuracy of a biodynamic drug response classifier in muscle-invasive bladder cancer (MIBC) patients undergoing neoadjuvant chemotherapy (NAC). DESIGN, SETTING, AND PARTICIPANTS: One hundred five consecutive bladder cancer patients suspected of having MIBC were screened in a multi-institutional prospective observational study (NCT03739177) from July 2018 to June 2020, of whom, 30 completed NAC and radical cystectomy. INTERVENTION(S): Biodynamic signatures from treatment-naïve fresh bladder tumor specimens obtained after transurethral resection were measured in living tumor fragments challenged by standard-of-care cytotoxins. Patients received gemcitabine and cisplatin or dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin per institutional guidelines and were followed through radical cystectomy. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: A 4-level classifier was developed to predict pathologic complete response (pCR) vs. incomplete response utilizing a one-left-out cross-validation protocol to minimize over-fitting. Area under the curve evaluated predictive utility. RESULTS: Thirty percent (9 of 30) achieved pCR. Utilizing the 4-level classifier, biodynamically ""favored"" (scoring ≥ 3) and ""strongly favored"" (scoring 4) regimens accurately predicted pCR at rates of 66.7% (4 of 6 patients) and 100% (4 of 4 patients), respectively. Biodynamically ""favored"" scores predicted pCR with 88% sensitivity and 95% negative predictive value, P < 0.0001. Only 5.0% (1 of 20 patients) achieved pCR from regimens scoring 1 or 2, indicating poor to no response from NAC. Area under the receiver operating curve was 96% (95% Confidence Interval: 79%-99%, P < 0.0001). Future direction involves validating this model prospectively. PRINCIPAL CONCLUSIONS: Biodynamic scoring accurately predicts response in MIBC patients receiving NAC and holds promise to substantially improve the scope of appropriate management intervention."	bladder
New synthetic nano-immunotherapy (OncoTherad®) for non-muscle invasive bladder cancer: Its synthesis, characterization and anticancer property.	Bacillus Calmette-Guérin (BCG)-based intravesical immunotherapy has been applied as gold standard treatment for high-risk non-muscle invasive bladder cancer (NMIBC) for almost half a century. However, several patients with high-risk disease experience relapse, including those whose condition has worsened and who failed to respond to BCG. Non-significant therapeutic options have been developed for these at-risk patients, for many years. Immunotherapies have shown promising outcomes for bladder cancer treatment. Accordingly, our research group developed the OncoTherad® (MRB-CFI-1) immunotherapy, which has shown positive outcomes in NMIBC treatment. The aim of the current study is to describe, in details, the physicochemical features and potential action mechanisms of OncoTherad® nano-immunotherapy, based on toll-like receptor 4 (TLR4)-mediated interferon and on RANK/RANKL signaling pathways, in animal model with NMIBC. Based on the current findings, OncoTherad® nano-immunotherapy did not have genotoxic effect on the investigated model and did not show signs of limiting local and/or systemic toxicity at therapeutic doses. OncoTherad® nano-immunotherapy was more effective than the BCG treatment, since it reduced by 70% the malignancy rate. Furthermore, it was possible identifying an important action mechanism of OncoTherad®, which was based on the modulation of TLR4-mediated interferon and RANK/RANKL signaling pathways that, altogether, were essential to reduce malignancy rate. OncoTherad® mechanisms in these pathways helped preventing tumor recurrence.	bladder
Noninvasive Multiplexed Analysis of Bladder Cancer-Derived Urine Exosomes via Janus Magnetic Microspheres.	Bladder cancer greatly endangers human health, and its early diagnosis is of vital importance. Exosomes, which contain proteins and nucleic acids related to their source cells, are expected to be an emerging biomarker for bladder cancer detection. Here, we propose a novel system for multiplexed analysis of bladder cancer-derived urine exosomes based on Janus magnetic microspheres as barcoded microcarriers. The microcarriers are constructed by droplet-templated coassembly of colloidal silica nanoparticles and magnetic nanoparticles under a magnetic field. The microcarriers possess one hemisphere with structural color and the other hemisphere with magneto-responsiveness. Benefiting from the unique structure, these Janus microcarriers could serve as barcodes and could move controllably in a sample solution, thus realizing the multiplex detection of exosomes with high sensitivity. Notably, the present platform is noninvasive since a urine specimen, as an ideal source of bladder cancer-derived exosomes, is employed as the sample solution. This feature, together with the good sensitivity, specificity, low sample consumption, and easy operation, indicates the great potential of the platform for bladder cancer diagnosis in clinical applications.	bladder
Identification of molecular subtypes based on liquid-liquid phase separation and cross-talk with immunological phenotype in bladder cancer.	BACKGROUND: Mounting evidence has demonstrated that an imbalance in liquid-liquid phase separation (LLPS) can induce alteration in the spatiotemporal coordination of biomolecular condensates, which plays a role in carcinogenesis and cachexia. However, the role of LLPS in the occurrence and progression of bladder cancer (BLCA) remains to be elucidated. Identifying the role of LLPS in carcinogenesis may aid in cancer therapeutics. METHODS: A total of 1,351 BLCA samples from six cohorts were retrieved from publicly available databases like The Cancer Genome Atlas, Gene Expression Omnibus, and ArrayExpress. The samples were divided into three distinct clusters, and their multi-dimensional heterogeneities were explored. The LLPS patterns of all patients were determined based on the LLPS-related risk score (LLPSRS), and its multifaceted landscape was depicted and experimentally validated at the multi-omics level. Finally, a cytotoxicity-related and LLPSRS-based classifier was established to predict the patient's response to immune checkpoint blockade (ICB) treatment. RESULTS: Three LLPS-related subtypes were identified and validated. The differences in prognosis, tumor microenvironment (TME) features, cancer hallmarks, and certain signatures of the three LLPS-related subtypes were validated. LLPSRS was calculated, which could be used as a prognostic biomarker. A close correlation was observed between clinicopathological features, genomic variations, biological mechanisms, immune infiltration in TME, chemosensitivity, and LLPSRS. Furthermore, our classifier could effectively predict immunotherapy response in patients with BLCA. CONCLUSIONS: Our study identified a novel categorization of BLCA patients based on LLPS. The LLPSRS could predict the prognosis of patients and aid in designing personalized medicine. Further, our binary classifier could effectively predict patients' sensitivity to immunotherapy.	bladder
Bladder Preservation for Muscle-Invasive Bladder Cancer With Variant Histology.	A growing body of evidence has shown bladder-preservation with chemo-radiotherapy achieves comparable survival to Radical Cystectomy (5-year OS 50%-70%) and superior quality of life outcomes for patients with muscle-invasive urothelial carcinoma of the bladder (UC). However, up to 55% of patients harbor variant histology and in this review we aim to clarify the role of bladder-preservation for this group. We first draw the distinction between urothelial carcinoma with divergent differentiation (UCDD) and non-urothelial carcinoma (NUC). UCDD is common, increasing in prevalence, and whilst each subtype may have its own characteristics current evidence suggests comparable outcomes with radical cystectomy and bladder-preservation. Non-urothelial carcinoma is a collection of distinct pathologies each deserving of its own management strategy. However, these tumors are rare, and evidence is generated from retrospective studies with significant inherent bias. Small cell carcinoma of the bladder has good evidence for bladder-preservation; however, other pathologies such as Squamous Cell Carcinoma and Adenocarcinoma are not well supported. We recommend careful multidisciplinary appraisal of the evidence for each subtype and honest patient discussion about the limited evidence before reaching management decisions. As we look to the future molecular-profiling may help better characterize these tumors and aid in treatment selection.	bladder
Rare Case of Intramural Urinary Bladder Leiomyoma.	Leiomyomas are the most common mesenchymal tumors of the urinary bladder. They account for 0.43% of all bladder tumors. Their incidence is 3 times higher in women than in men. There are approximately 250 cases described in the scientific literature, but none are of Caribbean males. The intramural location of the neoplasm described in this article was uncommon; only 7% of all the leiomyomas of the urinary bladder are found in this location. We present a case of a 65-year-old male with an intramural leiomyoma that was found incidentally during the evaluation of left lower-quadrant abdominal pain. The histopathological specimen that was taken at the time at the time of surgery showed a tumor with atypical smooth muscle cells indicative of a leiomyoma. The clinical presentation, radiographic imaging, and surgical management of this rare tumor are presented herein.	bladder
Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques.	Administration of a novel and selective small molecule integrin αvβ6 inhibitor, MORF-627, to young cynomolgus monkeys for 28 days resulted in the rapid induction of epithelial proliferative changes in the urinary bladder of 2 animals, in the absence of test agent genotoxicity. Microscopic findings included suburothelial infiltration by irregular nests and/or trabeculae of epithelial cells, variable cytologic atypia, and high mitotic rate, without invasion into the tunica muscularis. Morphologic features and patterns of tumor growth were consistent with a diagnosis of early-stage invasive urothelial carcinoma. Ki67 immunohistochemistry demonstrated diffusely increased epithelial proliferation in the urinary bladder of several monkeys, including those with tumors, and αvβ6 was expressed in some epithelial tissues, including urinary bladder, in monkeys and humans. Spontaneous urothelial carcinomas are extremely unusual in young healthy monkeys, suggesting a direct link of the finding to the test agent. Inhibition of integrin αvβ6 is intended to locally and selectively block transforming growth factor beta (TGF-β) signaling, which is implicated in epithelial proliferative disorders. Subsequent in vitro studies using a panel of integrin αvβ6 inhibitors in human bladder epithelial cells replicated the increased urothelial proliferation observed in monkeys and was reversed through exogenous application of TGF-β. Moreover, analysis of in vivo models of liver and lung fibrosis revealed evidence of epithelial hyperplasia and cell cycle dysregulation in mice treated with integrin αvβ6 or TGF-β receptor I inhibitors. The cumulative evidence suggests a direct link between integrin αvβ6 inhibition and decreased TGF-β signaling in the local bladder environment, with implications for epithelial proliferation and carcinogenesis.	bladder
Construction of an lncRNA model for prognostic prediction of bladder cancer.	OBJECTIVE: We aimed to investigate the role and potential mechanisms of long non-coding RNAs (lncRNAs) in bladder cancer (BC), as well as determine their prognostic value. METHODS: LncRNA expression data and clinical data from BC patients were downloaded from The Cancer Genome Atlas (TCGA) database. R software was used to carry out principal component analysis (PCA), differential analysis, and prognostic analysis. Lasso regression and multivariate Cox regression analyses were performed to identify potential prognostic genes. The expression of five identified genes and their correlation with prognosis were verified using TCGA and GSE13507 datasets. In addition, quantitative real-time polymerase chain reaction (qRT-PCR) was used to confirm the expression of these five genes in cell lines (two human BC cell lines and one human bladder epithelial cell line) and tissues (84 pairs of BC tissues and the corresponding paracancerous tissues). Risk scores that had been generated from the five genes and their prognostic ability were assessed by receiver operating characteristic (ROC) and Kaplan-Meier (KM) curves. Co-expressed genes were screened by WGCNA and analyzed by GO and KEGG, while functional enrichment and immune infiltration analyses were performed using STRING ( https://cn.string-db.org/ ) and TIMER2.0 ( http://timer.cistrome.org/ ) online tools, respectively. RESULTS: CYP4F8, FAR2P1, LINC01518, LINC01764, and DTNA were identified as potential prognostic genes. We found that these five genes were differentially expressed in BC tissue, as well as in BC cell lines, and were significantly correlated with the prognosis of BC patients. KM analysis considering risk scores as independent parameters revealed differences in overall survival (OS) by subgroups. The ROC curve revealed that a combined model consisting of all five genes had good predictive ability at 1, 3, and 5 years. GO and KEGG analyses of 567 co-expressed genes revealed that these genes were significantly associated with muscle function. CONCLUSION: LncRNAs can be good predictors of BC development and prognosis, and may act as potential tumor markers and therapeutic targets that may be beneficial in helping clinicians decide the most effective treatment strategies.	bladder
A Systematic Review and Meta-Analysis of Clinicopathologic Factors Predicting Upper Urinary Tract Recurrence After Radical Cystectomy for Urothelial Bladder Cancer.	To identify risk factors for upper urinary tract recurrence (UUTR) in patients treated with radical cystectomy (RC) for urothelial bladder carcinoma (UBC). The PubMed, Web of Science, and Cochrane Library were searched on March 2022 to identify relevant studies according to the Preferred Reporting Items for Systematic Review (PRISMA) statement. We included studies that provided multivariate logistic regression analyses. The pooled UUTR rate was calculated using a fixed effect model. We identified 235 papers, of which seven and 6 articles, comprising a total of 8981 and 8404 UBC patients, were selected for qualitative and quantitative analyses, respectively. Overall, 418 (4.65%) patients were diagnosed with UUTR within a median time of 1.4 to 3.1 years after RC. Risk factors for UUTR were surgical margin (hazard ratio [HR] 3.41, 95% confidence interval [CI] 2.59-4.49, P < .00001), preoperative hydronephrosis (HR: 1.74, 95% CI: 1.25-2.43, P = .001), ureteral margin (HR: 4.34, 95% CI: 2.75-6.85, P < .00001), and pT stage (HR: 2.69, 95% CI: 1.37-5.27, P < .004). Incorporation of established risk factors into a clinical prediction model might aid in the decision-making process regarding the intensity and type of surveillance protocols after RC as well as help determine the pretest probability of UUTR.	bladder
Identification and validation of a novel prognostic model based on platinum Resistance-related genes in bladder cancer.	BACKGROUND: The depth of response to platinum in urothelial neoplasm tissues varies greatly. Biomarkers that have practical value in prognosis stratification are increasingly needed. Our study aimed to select a set of BC (bladder cancer)-related genes involved in both platinum resistance and survival, then use these genes to establish the prognostic model. MATERIALS AND METHODS: Platinum resistance-related DEGs (differentially expressed genes) and tumorigenesis-related DEGs were identified. Ten most predictive co-DEGs were acquired followed by building a risk score model. Survival analysis and ROC (receiver operating characteristic) plot were used to evaluate the predictive accuracy. Combined with age and tumor stages, a nomogram was generated to create a graphical representation of survival rates at 1-, 3-, 5-, and 8-year in BC patients. The prognostic performance was validated in three independent BC datasets with platinum-based chemotherapy. The potential mechanism was explored by enrichment analysis. RESULTS: PPP2R2B, TSPAN7, ATAD3C, SYT15, SAPCD1, AKR1B1, TCHH, AKAP12, AGLN3, and IGF2 were selected for our prognostic model. Patients in high- and low-risk groups exhibited a significant survival difference with HR (hazard ratio) = 2.7 (p < 0.0001). The prognostic nomogram of predicting 3-year OS (overall survival) for BC patients could yield an AUC (area under the curve) of 0.819. In the external validation dataset, the risk score also has a robust predictive ability. CONCLUSION: A prognostic model derived from platinum resistance-related genes was constructed, we confirmed its value in predicting platinum-based chemotherapy benefits and overall survival for BC patients. The model might assist in therapeutic decisions for bladder malignancy.	bladder